Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
yanxiaojing_pp@hotmail.com
salinaofcmu@163.com
Show less
History+
Received
Accepted
Published Online
2025-07-30
2025-11-26
2026-01-23
PDF
(1162KB)
Abstract
Diffuse large B-cell lymphoma (DLBCL) can present with hyperlactatemia or even lactic acidosis (LA) as a rare but often underrecognized complication among hematologists. Patients diagnosed with DLBCL complicated by LA generally exhibit high mortality and a poor prognosis, even with therapeutic intervention. This report details two cases of DLBCL concurrently presenting with LA and provides a literature review. Our analysis of 19 published studies revealed a survival advantage in patients with an initial lactate levels of 5–14.9 mmol/L compared to those with levels of 15–24.9 mmol/L. Furthermore, the maximum lactate level correlated with survival, with higher values predicting shorter survival times. For type B LA, early initiation of chemotherapy-based treatment significantly improved patient survival compared to other treatment approaches (P = 0.026). Adjunctive treatments such as sodium bicarbonate, thiamine, and vitamin B may also be beneficial. Careful attention should also be paid to avoiding medications that can increase lactate levels.
Yu Jiao, Jingwen Zhang, Xiaojing Yan, Na Lin.
Diffuse large B-cell lymphoma combined with hyperlactatemia presents high mortality: case report and literature review.
MedScience, 2026, 20 (1) : 186-193 DOI:10.1007/s11684-025-1199-2
Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA. Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol2013; 87(2): 146–171
[2]
Liu QS, Harji F, Jones A, Tarnower AC.. Type B lactic acidosis: a rare oncological emergency. BMJ Case Rep2020; 13(3):
[3]
Suetrong B, Walley KR. Lactic acidosis in sepsis: it’s not all anaerobic: implications for diagnosis and management. Chest2016; 149(1): 252–261
[4]
Jin S, Chen X, Yang J, Ding J. Lactate dehydrogenase D is a general dehydrogenase for D-2-hydroxyacids and is associated with D-lactic acidosis. Nat Commun2023; 14(1): 6638
[5]
Jiang B. Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis2017; 4(1): 25–27
[6]
Vaupel P, Multhoff G. Revisiting the Warburg effect: historical dogma versus current understanding. J Physiol2021; 599(6): 1745–1757
[7]
Kobliakov VA. Tumor tissue acidosis as a factor determining the malignant phenotype and tumor resistance to chemotherapy. Cell Tissue Biol2024; 18(5): 489–502
[8]
Borde S, Matosevic S. Metabolic adaptation of NK cell activity and behavior in tumors: challenges and therapeutic opportunities. Trends Pharmacol Sci2023; 44(11): 832–848
[9]
Chen S, Xu Y, Zhuo W, Zhang L. The emerging role of lactate in tumor microenvironment and its clinical relevance. Cancer Lett2024; 590: 216837
[10]
Crane GM, Perkins AS. Leukemic presentation of diffuse large B-cell lymphoma: an unusual pattern associated with splenic involvement. Blood2017; 130(20): 2233
[11]
Wang E, Papavassiliou P, Wei Q, Wickham MQ, Cichon L, Proia AD. An Epstein-Barr virus-positive diffuse large B-cell lymphoma presenting as multi-organ failure: a catastrophic lymphomatosis with fulminant visceral organ dissemination resulting in a precipitous death in a 59-year-old female with no identifiable etiology for immunodeficiency. Pathol Res Pract2014; 210(1): 62–66
[12]
Hafner A, Eaton DB. Acute liver failure with severe lactic acidosis secondary to infiltrative diffuse large B-cell lymphoma: an imaging-negative presentation. Cureus2020; 12(8): e10110
[13]
Gkoufa A, Georgakopoulou VE, Lakiotaki E, Cholongitas E. An unusual presentation of diffuse large B-cell lymphoma. Cureus2022; 14(1): e20927
[14]
Kumar A, Raina V. Non-Hodgkins lymphoma with lactic acidosis at presentation: a case report of a rare oncologic emergency. Indian J Med Paediatr Oncol2014; 35(1): 83–85
[15]
Keller BC, Nussensveig D, Dowell JE. Diffuse large B-cell lymphoma in a hepatitis C virus-infected patient presenting with lactic acidosis and hypoglycemia. Am J Med Sci2010; 339(2): 202–204
[16]
Sanivarapu R, Upadrista PK, Otero-Colon J, Shah K, Cadet B, Tao Q, Iqbal J. An oncological emergency: severe type B lactic acidosis from Warburg effect in diffuse large B-cell lymphoma. Cureus2022; 14(7): e26557
[17]
Weeraddana P, Odujoko O, Bal S, Mannapperuma N, Maslak D, Gupta G. An elusive diagnosis: diffuse large B-Cell lymphoma masquerading as acute liver failure with persistent lactic acidosis. Am J Case Rep2023; 24: e941270
[18]
Mohammed TJ, Gosain R, Sharma R, Torka P. Lactic acidosis: a unique presentation of diffuse large B-cell lymphoma. BMJ Case Rep2019; 12(10): e230277
[19]
Hamada T, Kaku T, Mitsu S, Morita Y, Ohno N, Yamaguchi H. Lactic acidosis and hypoglycemia in a patient with gastric diffuse large B-cell lymphoma due to the Warburg effect. Case Rep Oncol2020; 13(2): 1047–1052
[20]
He Y, Ong J, Ong S. Refractory lactic acidosis and an approach to its management—a case report. J Crit Care Med (Targu Mures)2019; 5(2): 60–65
[21]
Arif H, Zahid S, Kaura A. Persistent lactic acidosis: thinking outside the box. Cureus2018; 10(5): e2561
[22]
Masood U, Sharma A, Nijjar S, Sitaraman K. B-cell lymphoma, thiamine deficiency, and lactic acidosis. Proc Bayl Univ Med Cent2017; 30(1): 69–70
[23]
Elhomsy GC, Eranki V, Albert SG, Fesler MJ, Parker SM, Michael AG, Griffing GT. “Hyper-warburgism, ” a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin’s lymphoma. J Clin Endocrinol Metab2012; 97(12): 4311–4316
[24]
Yu D, Tang X, Xue H, Ao Y, Xie Y, Li X. Paraneoplastic syndrome in malignant lymphoma: a case report. Heliyon2023; 9(8): e18968
[25]
Hoogwerf D, van Doorn J, Maartense E. The insulin-like growth factor-system in a patient with diffuse large B-cell non-Hodgkin’s lymphoma and lactic acidosis. Ann Clin Biochem2013; 50(2): 169–172
[26]
Al Maqrashi Z, Sedarous M, Pandey A, Ross C, Wyne A. Refractory hyperlactatemia and hypoglycemia in an adult with non-Hodgkin’s lymphoma: a case report and review of the Warburg effect. Case Rep Oncol2021; 14(2): 1159–1167
[27]
Kestler MH, Gardner EM, Cohn DL. Hepatic non-Hodgkin’s lymphoma with lactic acidosis in HIV-infected patients: report of 2 cases. J Int Assoc Physicians AIDS Care (Chic)2010; 9(5): 301–305
[28]
Tanios G, Aranguren IM, Goldstein JS, Patel CB. Diffuse large B-cell lymphoma: a metabolic disorder. Am J Case Rep2013; 14: 518–525
[29]
Chaba A, Fodil S, Lemiale V, Mariotte E, Valade S, Azoulay E, Zafrani L. Clinical Warburg effect in lymphoma patients admitted to intensive care unit. Ann Intensive Care2023; 13(1): 97
[30]
Sia P, Plumb TJ, Fillaus JA. Type B lactic acidosis associated with multiple myeloma. Am J Kidney Dis2013; 62(3): 633–637
[31]
Alfaifi A, Bahashwan S, Alsaadi M, Malhan H, Aqeel A, Al-Kahiry W, Almehdar H, Qadri I. Metabolic biomarkers in B-cell lymphomas for early diagnosis and prediction, as well as their influence on prognosis and treatment. Diagnostics (Basel)2022; 12(2): 394
[32]
Cao Y, Chen P, Cai M, Shi Q, Xu P, Wang L, He Y, Wang H, Zhao W. Prognostic impact of B-vitamins involved in one-carbon metabolism in patients with diffuse large B-cell lymphoma. Hematol Oncol2020; 38(4): 456–466
[33]
Hamaguchi R, Isowa M, Narui R, Morikawa H, Wada H. Clinical review of alkalization therapy in cancer treatment. Front Oncol2022; 12: 1003588
[34]
Halperin ML, Cheema-Dhadli S, Halperin FA, Kamel KS. Rationale for the use of sodium bicarbonate in a patient with lactic acidosis due to a poor cardiac output. Nephron J1994; 66(3): 258–261
[35]
Piha-Paul S, Simon G, Belani CP, Chao H, Gaspar K, Lee B, Dowlati A. A phase 1, open-label, dose-escalation study of L-DOS47 in combination with pemetrexed plus carboplatin in patients with stage IV recurrent or metastatic nonsquamous NSCLC. JTO Clin Res Rep2022; 3(11): 100408
[36]
Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, Klaerner G, Bushinsky DA. Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet2019; 394(10196): 396–406
[37]
Kraut JA, Madias NE. Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol2012; 8(10): 589–601
[38]
Wu D, Qi J, Dai H, Doods H, Abraham WM. Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: cardiopulmonary performance, oxygen transport and tissue inflammation. Clin Exp Pharmacol Physiol2010; 37(3): 337–342
[39]
De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med2006; 34(2): 403–408
[40]
Zanza C, Facelli V, Romenskaya T, Bottinelli M, Caputo G, Piccioni A, Franceschi F, Saviano A, Ojetti V, Savioli G, Longhitano Y. Lactic acidosis related to pharmacotherapy and human diseases. Pharmaceuticals (Basel)2022; 15(12): 1496